Protein arginine methyltransferase 3 (PRMT3), a type I arginine methyltransferase is localized predominantly in the cytoplasm and regulates different cellular functions. Nevertheless, PRMT3 also exhibits regulatory functions in the nucleus by interacting with the liver X receptor alpha (LXRα) and catalyzes asymmetric dimethylation modifications at arginine 3 of histone 4 (H4R3me2a). However, very little is known about the regulation of the versatile global regulator PRMT3 and how PRMT3 is translocated to the nucleus. In this study, we identified ZNF200, a hitherto uncharacterized protein, as a potential binding partner of PRMT3 through yeast two-hybrid screening. We confirmed the interaction of PRMT3 with ZNF200 using immunoprecipitation and in vitro pull-down experiments. GST pull-down experiments and molecular docking studies revealed that the N-terminal zinc finger domain of PRMT3 binds to the C-terminal zinc finger regions of ZNF200. Furthermore, the evolutionary conservation of the Znf domain of PRMT3 correlates with the emergence of ZNF200 in mammals. We found that ZNF200 stabilizes PRMT3 by inhibiting its proteasomal degradation. ZNF200, a nuclear-predominant protein, promotes the nuclear translocation of PRMT3, leading to the global increase of H4R3me2a modifications. These findings imply that ZNF200 is a critical regulator of the steady-state levels and nuclear and epigenetic functions of PRMT3.

中文翻译：

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未表征的蛋白 ZNF200 与 PRMT3 相互作用并有助于其稳定性和核转位。


蛋白精氨酸甲基转移酶 3 （PRMT3） 是一种 I 型精氨酸甲基转移酶，主要位于细胞质中，调节不同的细胞功能。然而，PRMT3 还通过与肝脏 X 受体 α （LXRα） 相互作用在细胞核中表现出调节功能，并催化组蛋白 4 （H4R3me2a） 精氨酸 3 处的不对称二甲基化修饰。然而，关于多功能全局调节因子 PRMT3 的调节以及 PRMT3 如何易位到细胞核，人们知之甚少。在这项研究中，我们通过酵母双杂交筛选确定了 ZNF200（一种迄今为止未表征的蛋白质）是 PRMT3 的潜在结合伴侣。我们使用免疫沉淀和体外沉降实验证实了 PRMT3 与 ZNF200 的相互作用。GST pull-down 实验和分子对接研究表明，PRMT3 的 N 端锌指结构域与 ZNF200 的 C 端锌指区域结合。此外，PRMT3 的 Znf 结构域的进化保守性与 ZNF200 在哺乳动物中的出现相关。我们发现 ZNF200 通过抑制蛋白酶体降解来稳定 PRMT3。ZNF200 是一种核为主蛋白，可促进 PRMT3 的核转位，导致 H4R3me2a 修饰的整体增加。这些发现表明 ZNF200 是 PRMT3 稳态水平以及核和表观遗传功能的关键调节因子。